Academic literature on the topic 'Adenosine diphosphate; ADP; Blood'
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Journal articles on the topic "Adenosine diphosphate; ADP; Blood"
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Poelstra, K., JF Baller, MJ Hardonk, and WW Bakker. "Demonstration of antithrombotic activity of glomerular adenosine diphosphatase [published erratum appears in Blood 1991 Oct 15;78(8):2163]." Blood 78, no. 1 (July 1, 1991): 141–48. http://dx.doi.org/10.1182/blood.v78.1.141.bloodjournal781141.
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We have demonstrated that reduced glomerular adenosine diphosphatase (ADPase) activity within the rat kidney is associated with an increased thrombotic tendency. To establish a possible causal relationship between these intraglomerular events, experiments were conducted to inhibit adenosine diphosphate (ADP) degradation without influencing other glomerular prothrombotic or antithrombotic mechanisms. Concurrently, we studied intraglomerular platelet aggregation. Two ways of selective inhibition of glomerular ADPase activity were applied: (1) by competitive substrates (ie, uridine diphosphate [UDP]), and (2) by the nondegradable ADP analogue ADP-beta-S. Both strategies were used during ex vivo alternate perfusion of kidneys with platelets and ADP (to test intraglomerular thrombotic tendency). Each group (n = 6) received different substrates or a combination of substrates. A significant increase in platelet aggregation was observed in kidneys after perfusion with platelets and ADP together with the competitive substrate UDP as compared to perfusions with platelets and ADP alone (78.5% +/- 9.8% v 27.9% +/- 11.4% glomeruli staining positive for platelets, P less than .005). In contrast, UDP alone had no effect on platelet aggregation. Other nucleoside polyphosphates (guanosine diphosphate and inosine triphosphate) were also effective as competitive substrates in the ex vivo perfusion model (n = 4). None of these substrates was capable of increasing ADP-induced aggregation when studied in vitro. In addition, ADP- beta-S also increased platelet aggregation in the perfusion model as compared with native ADP (P less than .005). These results show that selective reduction of ADP degradation in intact kidneys strongly promotes the intraglomerular proaggregatory condition. It can be concluded that glomerular ADPase exerts potent antithrombotic activity within the normal rat kidney.
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Poelstra, K., JF Baller, MJ Hardonk, and WW Bakker. "Demonstration of antithrombotic activity of glomerular adenosine diphosphatase [published erratum appears in Blood 1991 Oct 15;78(8):2163]." Blood 78, no. 1 (July 1, 1991): 141–48. http://dx.doi.org/10.1182/blood.v78.1.141.141.
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Abstract We have demonstrated that reduced glomerular adenosine diphosphatase (ADPase) activity within the rat kidney is associated with an increased thrombotic tendency. To establish a possible causal relationship between these intraglomerular events, experiments were conducted to inhibit adenosine diphosphate (ADP) degradation without influencing other glomerular prothrombotic or antithrombotic mechanisms. Concurrently, we studied intraglomerular platelet aggregation. Two ways of selective inhibition of glomerular ADPase activity were applied: (1) by competitive substrates (ie, uridine diphosphate [UDP]), and (2) by the nondegradable ADP analogue ADP-beta-S. Both strategies were used during ex vivo alternate perfusion of kidneys with platelets and ADP (to test intraglomerular thrombotic tendency). Each group (n = 6) received different substrates or a combination of substrates. A significant increase in platelet aggregation was observed in kidneys after perfusion with platelets and ADP together with the competitive substrate UDP as compared to perfusions with platelets and ADP alone (78.5% +/- 9.8% v 27.9% +/- 11.4% glomeruli staining positive for platelets, P less than .005). In contrast, UDP alone had no effect on platelet aggregation. Other nucleoside polyphosphates (guanosine diphosphate and inosine triphosphate) were also effective as competitive substrates in the ex vivo perfusion model (n = 4). None of these substrates was capable of increasing ADP-induced aggregation when studied in vitro. In addition, ADP- beta-S also increased platelet aggregation in the perfusion model as compared with native ADP (P less than .005). These results show that selective reduction of ADP degradation in intact kidneys strongly promotes the intraglomerular proaggregatory condition. It can be concluded that glomerular ADPase exerts potent antithrombotic activity within the normal rat kidney.
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Cattaneo, Marco, Christian Gachet, Jeanne-Pierre Cazenave, and Marian A. Packham. "Adenosine diphosphate (ADP) does not induce thromboxane A2 generation in human platelets." Blood 99, no. 10 (May 15, 2002): 3868–70. http://dx.doi.org/10.1182/blood-2002-01-0313.
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Darlington, Daniel N., Xiaowu Wu, Kevin L. Chang, James Bynum, and Andrew P. Cap. "Regulation of Platelet Function By Adenosine Receptors." Blood 134, Supplement_1 (November 13, 2019): 2348. http://dx.doi.org/10.1182/blood-2019-131129.
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Introduction: We have recently shown that severe trauma and hemorrhage lead to inhibition of platelet aggregation and an elevation in cyclic adenosine monophosphate (cAMP). Adenosine is one of the few humoral agents known to stimulate cAMP in platelets. Because adenosine is released from damaged tissue, it may contribute to the platelet dysfunction seen after severe trauma. Platelets have four adenosine receptors (A1, A2a, A2b and A3). These receptors are G-Protein Coupled Receptors and have been proposed to stimulate adenylyl cyclase and increase intracellular cAMP. Although studies have shown that stimulate A2a can inhibit platelet aggregation and elevate cAMP, there is little data elucidating the function of the other receptors. Objective: Define which adenosine receptors affects platelet aggregation and cAMP production. Methods: Platelet-rich plasma (PRP) was isolated from whole blood of human volunteers, and centrifuged at 200g for 10min. Light transmission aggregometry was performed using a plate reader (Synergy Neo2 Multimode Reader, BioTek) with constant agitation. PRP was stimulated with adenosine diphosphate (ADP) with or without various adenosine agonists or antagonists, including the non-metabolizable adenosine agonist 5-(N-ethyl-carboxamido) adenosine (NECA), antagonists to receptors A1 (DPCPX), A2a (Sch 58261), A2b (GS 6201) and A3 (MRS 1220), or agonists for A2a (CGS 21680) A2b (BAY 60-6583) or agonist A1 (CCPA), A2a (CGS 21680), A2b (Bay 60-6583), A3 (2-Cl-IB-Meca). Cyclic AMP was extracted from 100ul of PRP after adding 1ml of EtOH, 10mM ammonium formate, with 10ug/ml cGMP-Br as an internal control. Samples were centrifuged at 20K g for 10min, and supernatant dried. Samples were brought up in 200ul of 0.1% formic acid for analysis by Reverse Phase liquid chromatography/ Tandem Mass Spectroscopy (Quantiva, ThrermoFisher). N-8/group. Results: Adenosine diphosphate (100uM) leads to platelet aggregation (change in mAbsorbance units, Table 1). The adenosine agonist NECA inhibited aggregation to ADP and elevated cAMP in a dose dependent manner (pg/ml per 1000 plt, Table 1). Platelet aggregation was inhibited and cAMP was elevated after stimulation with agonists for adenosine receptor A2a agonist, but not A1, A2b, or A3 (Table 2). Antagonists for A2a, but not A1, A2b, A3, blocked NECA inhibition of ADP aggregation (Table 3). Agonist for adenosine receptor A2a inhibited the ADP-induced aggregation and elevated cAMP in a dose response manner (Table 4). Discussion: Adenosine inhibits platelet aggregation to ADP. The mechanism appears to be due to elevation in intracellular cAMP, and works through the A2a receptor. These data suggest that the A2a receptor could be potential target for a resuscitation strategy that could attenuate or prevent platelet dysfunction after trauma by preventing stimulation of adenylate cyclase and synthesis of cAMP. This study was funded by the US Army medical Research and Development Command. Disclosures No relevant conflicts of interest to declare.
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Cattaneo, Marco. "The platelet P2Y12 receptor for adenosine diphosphate: congenital and drug-induced defects." Blood 117, no. 7 (February 17, 2011): 2102–12. http://dx.doi.org/10.1182/blood-2010-08-263111.
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Abstract P2Y12, the Gi-coupled platelet receptor for adenosine diphosphate (ADP), plays a central role in platelet function. Patients with congenital P2Y12 defects display a mild to moderate bleeding diathesis, characterized by mucocutaneous bleedings and excessive post-surgical and post-traumatic blood loss. Defects of P2Y12 should be suspected when ADP, even at high concentrations (≥ 10μM), is unable to induce full, irreversible platelet aggregation. Tests that evaluate the degree of inhibition of adenylyl cyclase by ADP should be used to confirm the diagnosis. Drugs that inhibit P2Y12 are potent antithrombotic drugs, attesting the central role played by P2Y12 in platelet thrombus formation. Clopidogrel, the most widely used drug that inhibits P2Y12, is effective both in monotherapy and in combination with acetylsalicylic acid. The most important drawback of clopidogrel is its inability to inhibit adequately P2Y12-dependent platelet function in approximately one-third of patients who are therefore not protected from major cardiovascular events. New drugs, such as prasugrel and ticagrelor, which effectively inhibit P2Y12 in the majority of patients, proved to be more efficacious than clopdidogrel in preventing major cardiovascular events. Although they increase the incidence of major bleedings, the net clinical benefit is in favor of the new P2Y12 inhibitors.
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Goto, Shinya, Noriko Tamura, and Shunnosuke Handa. "Effects of adenosine 5′-diphosphate (ADP) receptor blockade on platelet aggregation under flow." Blood 99, no. 12 (June 15, 2002): 4644–46. http://dx.doi.org/10.1182/blood-2001-12-0284.
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Muhsin, A., M. T. Eusni Raha, M. N. Sabariah, A. K. Faraizah, H. Roshida, and M. S. Salmiah. "Impaired Platelet Aggregation to Adenosine Diphosphate (ADP) Agonist in National Blood Centre, Malaysia." Asian Journal of Epidemiology 5, no. 4 (September 15, 2012): 114–22. http://dx.doi.org/10.3923/aje.2012.114.122.
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Koessler, Juergen, Philipp Klingler, Marius Niklaus, Katja Weber, Angela Koessler, Markus Boeck, and Anna Kobsar. "The Impact of Cold Storage on Adenosine Diphosphate-Mediated Platelet Responsiveness." TH Open 04, no. 03 (July 2020): e163-e172. http://dx.doi.org/10.1055/s-0040-1714254.
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Abstract Introduction Cold storage of platelets is considered to contribute to lower risk of bacterial growth and to more efficient hemostatic capacity. For the optimization of storage strategies, it is required to further elucidate the influence of refrigeration on platelet integrity. This study focused on adenosine diphosphate (ADP)-related platelet responsiveness. Materials and Methods Platelets were prepared from apheresis-derived platelet concentrates or from peripheral whole blood, stored either at room temperature or at 4°C. ADP-induced aggregation was tested with light transmission. Activation markers, purinergic receptor expression, and P2Y12 receptor function were determined by flow cytometry. P2Y1 and P2X1 function was assessed by fluorescence assays, cyclic nucleotide concentrations by immunoassays, and vasodilator-stimulated phosphoprotein (VASP)-phosphorylation levels by Western blot analysis. Results In contrast to room temperature, ADP-induced aggregation was maintained under cold storage for 6 days, associated with elevated activation markers like fibrinogen binding or CD62P expression. Purinergic receptor expression was not essentially different, whereas P2Y1 function deteriorated rapidly at cold storage, but not P2Y12 activity. Inhibitory pathways of cold-stored platelets were characterized by reduced responses to nitric oxide and prostaglandin E1. Refrigeration of citrated whole blood also led to the attenuation of induced inhibition of platelet aggregation, detectable within 24 hours. Conclusion ADP responsiveness is preserved under cold storage for 6 days due to stable P2Y12 activity and concomitant disintegration of inhibitory pathways enabling a higher reactivity of stored platelets. The ideal storage time at cold temperature for the highest hemostatic effect of platelets should be evaluated in further studies.
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Rinder, CS, LA Student, JL Bonan, HM Rinder, and BR Smith. "Aspirin does not inhibit adenosine diphosphate-induced platelet alpha- granule release." Blood 82, no. 2 (July 15, 1993): 505–12. http://dx.doi.org/10.1182/blood.v82.2.505.505.
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Abstract The involvement of metabolites of arachidonic acid in platelet-dense granule secretion and secondary platelet-platelet interactions is well characterized. However, their role in heterotypic interactions dependent on alpha-granule secretion is less well understood. Using platelet-surface expression of P-selectin as a marker of alpha-granule secretion, we have shown that: (1) aspirin treatment of platelets at doses that block dense granule secretion does not inhibit alpha-granule secretion to adenosine diphosphate (ADP); (2) synergism between epinephrine and ADP in the induction of P-selectin expression is similarly unaffected by aspirin; and (3) the ability of P-selectin to mediate adhesion of activated platelets to monocytes and polymorphonuclear lymphocytes in whole blood is also unchanged by aspirin treatment. To further explore the mechanisms responsible for platelet alpha-granule secretion, we have shown that inhibition of Na+/H+ exchange by either acidification of the extracellular medium or amiloride treatment blocked ADP-induced P-selectin expression. In contrast, incubation with the platelet lipoxygenase inhibitor 5,8,11- eicosatrynoic acid, by itself and with aspirin, did not decrease ADP- induced P-selectin expression. We conclude that platelet alpha-granule secretion in response to ADP is dependent on intact Na+/H+ exchange but is independent of the lipoxygenase- and cyclooxygenase-dependent metabolites of arachidonic acid.
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Rinder, CS, LA Student, JL Bonan, HM Rinder, and BR Smith. "Aspirin does not inhibit adenosine diphosphate-induced platelet alpha- granule release." Blood 82, no. 2 (July 15, 1993): 505–12. http://dx.doi.org/10.1182/blood.v82.2.505.bloodjournal822505.
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The involvement of metabolites of arachidonic acid in platelet-dense granule secretion and secondary platelet-platelet interactions is well characterized. However, their role in heterotypic interactions dependent on alpha-granule secretion is less well understood. Using platelet-surface expression of P-selectin as a marker of alpha-granule secretion, we have shown that: (1) aspirin treatment of platelets at doses that block dense granule secretion does not inhibit alpha-granule secretion to adenosine diphosphate (ADP); (2) synergism between epinephrine and ADP in the induction of P-selectin expression is similarly unaffected by aspirin; and (3) the ability of P-selectin to mediate adhesion of activated platelets to monocytes and polymorphonuclear lymphocytes in whole blood is also unchanged by aspirin treatment. To further explore the mechanisms responsible for platelet alpha-granule secretion, we have shown that inhibition of Na+/H+ exchange by either acidification of the extracellular medium or amiloride treatment blocked ADP-induced P-selectin expression. In contrast, incubation with the platelet lipoxygenase inhibitor 5,8,11- eicosatrynoic acid, by itself and with aspirin, did not decrease ADP- induced P-selectin expression. We conclude that platelet alpha-granule secretion in response to ADP is dependent on intact Na+/H+ exchange but is independent of the lipoxygenase- and cyclooxygenase-dependent metabolites of arachidonic acid.
Dissertations / Theses on the topic "Adenosine diphosphate; ADP; Blood"
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Webb, Rachel J. "Characterisation of P2-receptors on human platelets." Thesis, University of Oxford, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.342989.
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Pacheco-Rodriguez, Gustavo. "Synthesis, purification and characterization of small mono(ADP-ribosyl)ated molecules in the ADP-ribose elongation reaction catalyzed by poly(ADP-ribose)polymerase." Thesis, North Texas State University, 1993. https://digital.library.unt.edu/ark:/67531/metadc798168/.
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The ADP-ribose elongation catalyzed by poly(ADP-ribose) polymerase (PARP) [EC 2.2.2.30] has been partially characterized utilizing mono (ADP-ribosyl)ated polyamines. Arginine methyl ester (AME)-(ADP-ribose) and agmatine (AGMT)-(ADP-ribose) were synthesized enzymatically with a eukarytic mono(ADP-ribosyl) transferase and cholera toxin, respectively.
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Cervantes-Laurean, Daniel. "Preparation and Characterization of Model Conjugates for the Study of Proteins Modified by ADP-ribose." Thesis, University of North Texas, 1992. https://digital.library.unt.edu/ark:/67531/metadc935701/.
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Modification of proteins by ADP-ribose has been shown to be a versatile modification with respect to the amino acid side chain. The results described here will allow the study of the biological importance of ADP-ribose glycation and also allow differentiation on crude extracts between enzymatic modifications from protein ADP-ribose glycation that can occur due to the presence of NAD glycohydrolases.
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Alvarez-Gonzalez, Rafael. "Complex polymers of ADP-ribose occur in vitro and in vivo." Thesis, North Texas State University, 1985. https://digital.library.unt.edu/ark:/67531/metadc798086/.
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The work presented here included the development of a highly sensitive method to estimate the size and complexity of poly(ADP-ribose). This involved radiolabeling of the precursor pools, purification of polymers using a boronate resin, polymer fractionation according to size by molecular sieve chromatography and analysis of polymer complexity by enzymatic digestion to nucleotides which were quantified by strong anion exchange chromatography.
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Poole, Alastair W. "Responses of equine blood platelets induced by adenosine 5'-diphosphate." Thesis, University of Cambridge, 1992. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.260575.
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Scase, Timothy John. "Blood platelet responses induced by adenosine 5'-diphosphate : functional and molecular studies." Thesis, University of Cambridge, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.624899.
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Loflin, Paul T. (Paul Tracey). "Identification of Endogenous Substrates for ADP-Ribosylation in Rat Liver." Thesis, University of North Texas, 1992. https://digital.library.unt.edu/ark:/67531/metadc277847/.
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Bacterial toxins have been shown to modify animal cell proteins in vivo with ADPR. Animal cells also contain endogenous enzymes that can modify proteins. Indirect evidence for the existence in vivo of rat liver proteins modified by ADPR on arginine residues has been reported previously. Presented here is direct evidence for the existence of ADP-ribosylarginine in rat liver proteins. Proteins were subjected to exhaustive protease digestion and ADP-ribosyl amino acids were isolated by boronate chromatography.
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Nylander, Sven. "Thrombin/ADP-induced platelet activation and drug intervention /." Linköping : Univ, 2005. http://www.bibl.liu.se/liupubl/disp/disp2005/med885s.pdf.
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Chen, Hai-Ying. "Studies on Poly (ADP-ribose) Synthesis in Lymphocytes of Systemic Lupus Erythematosus Patients." Thesis, University of North Texas, 1991. https://digital.library.unt.edu/ark:/67531/metadc501263/.
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A method for assaying poly (ADP-ribose) polymerase (PADPRP) activity in lymphocytes of systemic lupus erythematosus (SLE) patients has been developed. Using this method, PADPRP activity has been studied in lymphocytes from 15 patients and 13 controls. The mean activity in SLE lymphocytes was significantly lower than that in controls and 60% of the SLE patients demonstrated activities below the minimum of the control population. Possible mechanisms for this altered metabolism were investigated. The Km app of PADPRP for NAD; size distribution, branch frequency, and rates of turnover of polymers; competition for substrate; and number of PADPRP molecules were studied. The data demonstrated that SLE lymphocytes have a decreased synthetic capacity rather than alterations in the substrate or in turnover of the product.
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Croset, Amélie. "Identification et caractérisation des mécanismes d'action des molécules appats, les SiDNA, dans l'inhibition des voies de réparation des cassures simple-brin." Thesis, Paris 11, 2013. http://www.theses.fr/2013PA11T018.
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La plupart des traitements anticancéreux, comme la chimiothérapie ou la radiothérapie, sont cytotoxiques et causent des dommages à l'ADN dans le but d’induire la mort des cellules tumorales. Cependant, l’efficacité d’activité de réparation de l'ADN des tumeurs entraine des résistances intrinsèques et acquises aux traitements. L'une des étapes précoces de la réparation de l’ADN est le recrutement de protéines au niveau du site de dommage. Ce recrutement est coordonné par une cascade de modifications et est contrôlé par des protéines senseurs telles que la protéine kinase ADN dépendante (DNA-PK) et / ou la poly (ADP- ribose) polymérase (PARP). Dans ce manuscrit, nous avons identifié et caractérisé le mécanisme d'action de petites molécules d'ADN (les siDNA), mimant des cassures double brin (appelé Dbait) ou simple brin (appelé Pbait), dans l’inhibition des voies de réparation des cassures simple brin (SSBR/BER). Nous démontrons que les molécules Dbait recrutent et activent à la fois PARP et DNA-PK, contrairement aux molécules Pbait qui ne recrutent que la PARP. L'étude comparative de ces deux molécules permet d'analyser les rôles respectifs des deux voies de signalisation: les deux molécules recrutent les protéines impliquées dans la voie de réparation des cassures simple brin (comme PARP, PCNA et XRCC1) et empêchent leurs recrutements aux niveaux des lésions chromosomiques. Les molécules Dbait inhibent par ailleurs le recrutement des protéines impliquées dans la voie de réparation des cassures double brin (NHEJ et HR). Pbait et Dbait désorganisent la réparation de l’ADN et sensibilisent les cellules tumorales aux traitements. L’inhibition de la réparation des cassures simple brin semble dépendre d’un piégeage des protéines directement sur les siDNA ou indirectement sur les polymères PAR. L’inhibition des voies de réparation des cassures double brin (DSB) semble par contre se faire de façon indirecte ; cette inhibition résulterait plutôt de la phosphorylation des protéines de réparation des DSB de part l’activation de DNA-PK. Les molécules Dbait et Pbait induisent un effet de létalité synthétique des cellules tumorales BRCA mutées. Cependant, la mutation BRCA semble être suffisante mais non nécessaire pour induire la sensibilité des cellules tumorales aux traitements Dbait. En effet, nous avons démontré que les molécules Dbait peuvent aussi sensibiliser les cellules ne présentant pas de mutation BRCA mais ayant toutefois une forte instabilité génétique. Nous avons trouvé une corrélation entre le niveau basal de protéines de réparation de l'ADN (ɣH2AX, PARP et PAR), le taux basal de cassures à l’ADN, la présence de micronoyaux (MN) et la sensibilité des cellules tumorales au traitement Dbait. Nous avons émis l’hypothèse que cette instabilité génétique, déterminé par la quantification de MN dans des biopsies tumorales, pourrait être un biomarqueur prédictif de l’effet du Dbait, non seulement dans les cancers du sein, mais aussi dans les glioblastomes, les mélanomes, les mélanomes uvéaux et les cancers du côlonMost conventional cancer treatments, such as chemotherapy or radiotherapy, are cytotoxic and cause DNA damages in the tumoral treated cells, which ultimately lead to their death. However, several intrinsic and acquired resistances of tumors to these treatments are due to the tumor efficient DNA repair activities. One of the major early steps of DNA repair is the recruitment of repair proteins at the damage site and this is coordinated by a cascade of modifications controlled by sensor proteins such as DNA-dependent protein kinase (DNA-PK) and/or poly (ADP-ribose) polymerase (PARP). In this manuscript, we identify and characterize the mechanism of action of short interfering DNA molecules (siDNA), mimicking double-strand breaks (called Dbait) or single-strand breaks (called Pbait) in Single Strand Break Repair pathway (SSBR/BER) inhibition. We demonstrate that Dbait bound and induced both PARP and DNA-PK activities, whereas Pbait acts only on PARP. The comparative study of the two molecules allows analysis of the respective roles of the two signaling pathways: both molecules recruit proteins involved in single-strand break repair (such as PARP, XRCC1 and PCNA) and prevent their recruitment at chromosomal damage. Dbait, but not Pbait, also inhibits recruitment of proteins involved in double-strand break (DSB) repair. By these ways, Pbait and Dbait disorganized DNA repair, thereby sensitizing cells to treatments. SSB repair inhibition depends upon a direct trapping of the main proteins on both molecules and an indirect trapping in PAR polymers. DSB repair inhibition may be indirect, resulting from the phosphorylation of DSB repair proteins by activated DNA-PK. The DNA repair inhibition by both molecules is confirmed by their synthetic lethality with BRCA mutations tumoral cell lines. However, BRCA mutation could be sufficient but not necessary to induce breast cancer cell lines and tumors sensitivity to Dbait treatment. In fact, we demonstrate that Dbait molecules could also have a stand-alone effect in BRCA wild type cells with a high genetic instability. We found a correlation between DNA repair proteins basal level (ɣH2AX, PARP and PAR), DNA break basal level, presence of micronucleus (MN) and tumoral cell lines sensitivity to Dbait treatment. We hypothesis that this genetic instability, determined by MN in tumor biopsies, could be a predictive biomarker of Dbait stand-alone effect, not only in breast cancer treatment, but also in glioblastoma, melanoma, uveal melanoma and colon cancer treatment
Books on the topic "Adenosine diphosphate; ADP; Blood"
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1945-, Richter Ch, ed. ADP-ribosylation of proteins: Enzymology and biological significance. Berlin: Springer-Verlag, 1987.
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1948-, Poirier Guy G., and Moreau Pierre 1952-, eds. ADP-ribosylation reactions. New York: Springer-Verlag, 1992.
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Alvarez-Gonzalez, R. Adp-Ribosylation Reactions: From Bacterial Pathogenesis To Cancer. Springer, 2012.
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K, Jacobson Myron, and Jacobson Elaine L, eds. ADP-ribose transfer reactions: Mechanisms andbiological significance. New York: Springer-Verlag, 1989.
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ADP-Ribose Transfer Reactions: Mechanisms and Biological Significance. Springer, 2012.
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Jacobson, Myron K., and Elaine L. Jacobson. ADP-Ribose Transfer Reactions: Mechanisms and Biological Significance. Springer, 2012.
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Alvarez-Gonzalez, R. ADP-Ribosylation Reactions: From Bacterial Pathogenesis to Cancer (Developments in Molecular and Cellular Biochemistry). Springer, 1999.
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Friedrich, Haag, Koch-Nolte Friedrich, and International Workshop on the Biological Significance of Mono ADP-Ribosylation in Animal Tissues (1996 : Hamburg, Germany), eds. ADP-ribosylation in animal tissues: Structure, function, and biology of mono (ADP-ribosyl) transferases and related enzymes. New York: Plenum, 1997.
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(Editor), Friedrich Haag, and Friedrich Koch-Nolte (Editor), eds. ADP Ribosylation in Animal Tissues: Structure, Function, and Biology of Mono (ADP-Ribosyl) Transferases and Related Enzymes (Advances in Experimental Medicine and Biology). Springer, 1997.
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Koch-Nolte, Friedrich, and Friedrich Haag. ADP-Ribosylation in Animal Tissues: Structure, Function, and Biology of Mono Transferases and Related Enzymes. Springer, 2012.
Find full textBook chapters on the topic "Adenosine diphosphate; ADP; Blood"
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Williams, Diane P., Patricia Bacha, Vicki Kelley, Terry B. Strom, and John R. Murphy. "Adenosine Diphosphate Ribosylation of Elongation Factor-2 as a Therapeutic Target: Genetic Construction and Selective Action of a Diphtheria Toxin-Related Interleukin-2 Fusion Protein." In ADP-Ribose Transfer Reactions, 478–86. New York, NY: Springer US, 1989. http://dx.doi.org/10.1007/978-1-4615-8507-7_89.
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Becker, Richard C., and Frederick A. Spencer. "Aspirin." In Fibrinolytic and Antithrombotic Therapy. Oxford University Press, 2006. http://dx.doi.org/10.1093/oso/9780195155648.003.0012.
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Aspirin, considered the prototypic platelet antagonist, has been available for over a century and currently represents a mainstay both in the prevention and treatment of vascular events that include stroke, myocardial infarction, peripheral vascular occlusion, and sudden death. Aspirin irreversibly acetylates cyclooxygenase (COX), impairing prostaglandin metabolism and thromboxane A2 (TXA2) synthesis. As a result, platelet aggregation in response to collagen, adenosine diphosphate (ADP), and thrombin (in low concentrations) is attenuated (Roth and Majerus, 1975). Because aspirin more selectively inhibits COX-1 activity (found predominantly in platelets) than COX-2 activity (expressed in tissues following an inflammatory stimulus), its ability to prevent platelet aggregation is seen at relatively low doses, compared with the drug’s potential antiinflammatory effects, which require much higher doses (Patrono, 1994). Several alternative mechanisms of platelet inhibition by aspirin have been proposed, including: (1) inhibition of platelet activation by neutrophils and (2) enhanced nitric oxide production. In addition, aspirin may prevent the progression of atherosclerosis by protecting low-density lipoprotein (LDL) cholesterol from oxidation and scavenging hydroxyl radicals. Following oral ingestion, aspirin is promptly absorbed in the proximal gastrointestinal (GI) tract (stomach, duodenum), achieving peak serum levels within 15 to 20 minutes and platelet inhibition within 40 to 60 minutes. Enteric-coated preparations are less well absorbed, causing an observed delay in peak serum levels and platelet inhibition to 60 and 90 minutes, respectively. The antiplatelet effect occurs even before acetylsalicylic acid is detectable in peripheral blood, probably from platelet exposure in the portal circulation. The plasma concentration of aspirin decays rapidly with a circulating half-life of approximately 20 minutes. Despite the drug’s rapid clearance, platelet inhibition persists for the platelet’s life span (7 ± 2 days) due to aspirin’s irreversible inactivation of COX-1. Because 10% of circulating platelets are replaced every 24 hours, platelet activity (bleeding time, primary hemostasis) returns toward normal (≥50% activity) within 5 to 6 days of the last aspirin dose (O’Brien, 1968). A single dose of 100 mg of aspirin effectively reduces the production of TXA2 in many (but not all) individuals.
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Godeau, Francois, and S. S. Koide. "Xenopus Mono(Adenosine Diphosphate Ribosyl) Transferase: Purification, Assay, and Properties." In ADP-Ribosylation, DNA Repair and Cancer, 111–18. CRC Press, 2020. http://dx.doi.org/10.1201/9781003079491-12.
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Webert, Kathryn E., and John G. Kelton. "Disorders of platelet number and function." In Oxford Textbook of Medicine, 4506–18. Oxford University Press, 2010. http://dx.doi.org/10.1093/med/9780199204854.003.220603.
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Platelets are released from megakaryocytes in the bone marrow and circulate for 5 to 10 days before being cleared by the cells of the reticuloendothelial system. They play a critical role in haemostasis, with key features being (1) adhesion—when the wall of a blood vessel is damaged, platelets adhere to exposed collagen and other components of the subendothelium via the glycoprotein Ib receptor and other adhesive receptors; followed by (2) activation—release of thrombin, adenosine diphosphate, and arachidonic acid, which is converted by a cascade of enzymes into platelet activating agents including thromboxane A...
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Becker, Richard C., and Frederick A. Spencer. "Clopidogrel." In Fibrinolytic and Antithrombotic Therapy. Oxford University Press, 2006. http://dx.doi.org/10.1093/oso/9780195155648.003.0013.
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Clopidogrel, a thienopyridine derivative, is a novel platelet antagonist that is several times more potent than ticlopidine but associated with fewer adverse effects. After repeated 75-mg oral doses of clopidogrel, plasma concentrations of the parent compound, which has no platelet-inhibiting effect, are very low. Clopidogrel is extensively metabolized in the liver. The main circulating metabolite is a carboxylic acid derivative with a plasma elimination half-life of 7.7 ± 2.3 hours. Approximately 50% of an oral dose is excreted in the urine and the remaining 50% in feces over the following 5 days. Dose-dependent inhibition of platelet aggregation is observed 2 hours after a single oral dose of clopidogrel, with a more significant inhibition achieved with loading doses (≥300 mg) by approximately 6 hours. Repeated doses of 75 mg of clopidogrel per day inhibit adenosine diphosphate (ADP)-mediated aggregation, with steady state being reached between day 3 and day 7. At steady state, the average inhibition to ADP is between 40% and 60%. Based on ex vivo studies, clopidogrel is approximately 100-fold more potent than ticlopidine. There are no cumulative antiplatelet effects with prolonged oral administration. The combined administration of clopidogrel (300 mg loading dose) and aspirin yields a readily discernible platelet-inhibiting effect within 90 to 120 minutes. Clopidogrel selectively inhibits the binding of ADP to its platelet receptor (P2Y12) and the subsequent G-protein–linked mobilization of intracellular calcium and activation of the glycoprotein (GP)IIb/IIIa complex (Gachet et al., 1992). The specific receptor has been cloned and is abundantly present on the platelet surface (Hollopter et al., 2001). Clopidogrel has no direct effect on cyclooxygenase, phosphodiesterase, or adenosine uptake. Clopidogrel is rapidly absorbed following oral administration with peak plasma levels of the predominant circulating metabolite occurring approximately 60 minutes later. Administration with meals does not significantly modify the bioavailability of clopidogrel. The available information suggests that clopidogrel offers safety advantages over ticlopidine, particularly with regard to bone marrow suppression and other hematologic abnormalities. Although thrombotic thrombocytopenic purpura (TTP) has been reported with clopidogrel (Bennett et al., 2000), its occurrence (11 cases per 3 million patients treated) is rare, and has not been reported in randomized clinical trials performed to date.
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Becker, Richard C., and Frederick A. Spencer. "Aggrenox and Cilostazol." In Fibrinolytic and Antithrombotic Therapy. Oxford University Press, 2006. http://dx.doi.org/10.1093/oso/9780195155648.003.0015.
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The dipyridamole component of Aggrenox and cilostazol, both phosphodiesterase inhibitors, are used predominantly in patients with peripheral vascular and cerebrovascular disease. Aggrenox is a combination platelet antagonist that includes aspirin (25 mg) and dipyridamole (200 mg extended-release preparation). It is typically taken twice daily. Aspirin’s mechanism of action has been discussed previously. Dipyridamole inhibits cyclic adenosine monophosphate (cAMP)-phosphodiesterase (PDE) and cyclic-3´, 5´- guanylate monophospate (GMP)-PDE (Bunag et al., 1964). The pharmacokinetic profile of aspirin has been summarized previously. Peak dipyridamole levels in plasma are achieved within several hours of oral administration (400 mg dose of Aggrenox). Extensive metabolism via conjugation with glucuronic acid occurs in the liver. There are no significant pharmacokinetic interactions between aspirin and dipyridamole coadministered as Aggrenox. Dipyridamole inhibits platelet aggregation by two distinct mechanisms. First, it attenuates adenosine uptake into platelets (as well as endothelial cells and erythrocytes). The resulting increase elicits a rise in cellular adenylate cyclase concentrations, resulting in elevated cAMP levels, which inhibit platelet activation to several agonists, including adenosine diphosphate (ADP), collagen, and platelet-activating factor. Dipyridamole also inhibits PDE. The subsequent increase in cAMP elevates nitric oxide concentration, facilitating platelet inhibitory potential (Eisert, 2001). The European Stroke Prevention Study (ESPS)-2 reported that 79.9% of patients experienced at least one on-treatment adverse event. The most common side effects were gastrointestinal complaints and headache. Dipyridamole has vasodilatory effects and should be used with caution in patients with severe coronary artery disease in whom episodes of angina pectoris may increase. Patients receiving Aggrenox should not be given adenosine for myocardial perfusion studies. Plasma concentrations of dipyridamole are approximately 40% higher in patients greater than 65 years of age compared with younger individuals. Aggrenox has not been studied in patients with acute coronary syndrome (ACS). The ESPS-2 included 6,602 patients with ischemic stroke (76% of the total population) or transient ischemic attack who were randomized to receive Aggrenox, dipyridamole alone, aspirin alone, or placebo. Aggrenox reduced the risk of stroke by 22.1% compared with aspirin and by 24.4% compared with dipyridamole. Both differences were statistically significant (p = .008 and p = .002, respectively) (Diener et al., 1996).
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Dalton, David R. "Roots, Shoots, Leaves, and Grapes." In The Chemistry of Wine. Oxford University Press, 2018. http://dx.doi.org/10.1093/oso/9780190687199.003.0015.
Full textAbstract:
As noted earlier and as anticipated by Charles and Francis Darwin it has been argued that plants sense the direction of gravity (gravitropism) by movement of starch granules found in cells called statocytes that contain compartments (organelles) called statoliths. The synthesis of statoliths appears to occur in the plastid (plant organelle) compartments called amyloplasts (Figure 7.1, 1). It has been suggested that this gravitropic signal then leads to movement of plant hormones such as indole-3-acetic acid (auxin) (Figure 7.2), through the phloem opposite to the pull of gravity to promote stem growth. Chloroplasts (Figure 7.1, 2) are cell compartments (plastids or organelles) in which photosynthesis is carried out. The process of photosynthesis, discussed more fully later, is accompanied by the production of adenosine triphosphate (ATP) from adenosine diphosphate (ADP) and inorganic phosphate (Pi) (Figure 7.3). ATP is consumed and converted to ADP and Pi in living systems. The cycle of production and consumption allows ATP to serve as an “energy currency” to pay for the reactions in living systems. Beyond this generally recognized critical function of chloroplasts, it has recently been pointed out that light/ dark conditions affect alternative splicing of genes which may be necessary for proper plant responses to varying light conditions. The organelles or plastids which contain the pigments for photosynthesis and the amyloplasts that store starch are only two of many kinds of plastids. Other plastids, leucoplasts for example, hold the enzymes for the synthesis of terpenes, and elaioplasts store fatty acids. Apparently, all plastids are derived from proplastids which are present in the pluripotent apical and root meristem cells. The cell wall (Figure 7.1, 3) is the tough, rigid layer that surrounds cells. It is located on the outside of the flexible cell membrane, thus adding fixed structure. A representation of a portion of the cell wall (as made up of cellulose and peptide cross-linking) is shown below in Figure 7.7. The cells will have different sizes as a function of where they are found (e.g., leaf, stalk, root), but in every case, the cell wall limits the size of the membrane that lies within.
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Becker, Richard C., and Frederick A. Spencer. "Platelet Glycoprotein IIb/IIIa Receptor Antagonists." In Fibrinolytic and Antithrombotic Therapy. Oxford University Press, 2006. http://dx.doi.org/10.1093/oso/9780195155648.003.0014.
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The glycoprotein (GP) IIb/IIIa (αIIb/β3) receptor totalling 50,000 to 70,000 copies per platelet represents a common pathway for platelet aggregation in response to a wide variety of biochemical and mechanical stimuli. Accordingly, it represents an attractive target for pharmacologic inhibition that can be applied to patients with acute coronary syndromes. The evolution of GPIIb/IIIa receptor antagonists began with murine monoclonal antibodies and subsequently expanded to include small peptide or nonpeptide molecules with structural similarities to fibrinogen. There are three intravenous GPIIb/IIIa receptor antagonists that have been approved by the U.S. Food and Drug Administration: . . . • Abciximab (ReoPro) . . . . . . • Tirofiban (Aggrastat) . . . . . . • Eptifibatide (Integrilin) . . . Abciximab (ReoPro) is the Fab fragment of the chimeric human–murine monoclonal antibody c7E3. Following an intravenous bolus, free plasma concentrations of abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second-phase half-life of 30 minutes, representing rapid binding to the platelet GPIIb/IIIa receptor. Abciximab remains in the circulation for 10 or more days in the platelet-bound state. Intravenous administration of abciximab in doses ranging from 0.15 mg/kg to 0.3 mg/kg produces a rapid dose-dependent inhibition of platelet aggregation in response to adenosine diphosphate (ADP). At the highest dose, 80% of platelet GPIIb/IIIa receptors are occupied within 2 hours and platelet aggregation, even with 20 μM ADP, is completely inhibited. Sustained inhibition is achieved with prolonged infusions (12 to 24 hours) and low-level receptor blockade is present for up to 10 days following cessation of the infusion; however, platelet inhibition during infusions beyond 24 hours has not been well characterized. Platelet aggregation in response to 5 μM ADP returns to greater than or equal to 50% of baseline within 24 hours of drug cessation. In nearly 2,100 patients undergoing either balloon coronary angioplasty or atherectomy at high risk for ischemic (thrombotic) complications, a bolus of abciximab (0.25 mg/kg) followed by a 12-hour continuous infusion (10 μg/min) reduced the occurrence of death, the occurrence myocardial infarction (MI), or the need for an urgent intervention (repeat angioplasty, stent placement, balloon pump insertion, or bypass grafting) by 35% (EPIC Investigators, 1994).
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"Commentary on and reprint of Born GVR, Aggregation of blood platelets by adenosine diphosphate and its reversal, in Nature (1962) 194:927–929." In Hematology, 937–39. Elsevier, 2000. http://dx.doi.org/10.1016/b978-012448510-5.50177-1.
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LICHTMAN, M., J. SPIVAK, L. BOXER, S. SHATTIL, and E. HENDERSON. "Commentary on and reprint of Born GVR, Aggregation of blood platelets by adenosine diphosphate and its reversal, in Nature (1962) 194:927–929." In Hematology, 937–39. Elsevier, 2000. http://dx.doi.org/10.1016/b978-012448510-5/50177-1.
Full textConference papers on the topic "Adenosine diphosphate; ADP; Blood"
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Chamone, D. A. F., M. Ivany-Silva, C. Cassaro, G. Bellotti, C. Massumoto, and A. Y. Hoshikawa-Fujimura. "GUARANA (Paullinia cupana) INHIBITS AGGREGATION IN WHOLE BLOOD." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1644553.
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Guarana, a methylxanthine obtained from the seeds of Paullinia cupana has been largely used in the Amazon region by native indians during centuries as stimulant. We evaluated the effect of guarana on ex-vivo and in vitro platelet aggregation induced by adenosine-5-diphosphate (ADP) in human and rat whole blood with an impedance (Chrono-Log, model 500) and in their platelet rich plasma (PRP) with an optical aggregometer (Chrono-Log, model 440). Ex-vivo studies were carried out after single oral intake of guarana. Seven healthy volunteers (5 male and 2 female) aged 19-26 years who had taken no drugs for 10 days before, ingested 8gm of crude powder of guarana. Blood samples were drawn before and 1 hour after guarana intake. We observed a significative inhibition of platelet aggregation in whole blood meanwhile PRP was un changed as compared to basal values. In vitro studies were performed in whole blood and PRP from human volunteers and male Wis-tar rats. The combined effect of guarana and adenosine was also studied. A control aggregation was always run with saline. The results demonstrated an inhibition statistically significative (p < 0.001) of platelet aggregation in whole blood. Differently from whole blood the PRP with the same concentration of guarana did not result in inhibition of ADP induced aggregation when eva luated with the impedance method. The blood incubation with adenosine and guarana resulted in synergistic inhibitory effect that was much more strinking in whole blood than in PRP. Guarana fails to inhibit aggregation of rat platelets.Our results demonstrate that guarana prevents platelet aggregation in whole blood which depends on red blood cells, probably involving adenosine.
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Nelson, S. D., A. J. Moriarty, R. Hughes, and K. Balnave. "TRANSITORY INFLUENCE OF FIBRINOGEN/FIBRIN DEGRADATION PRODUCTS (FDPs) ON PLATELET AGGREGATION." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1644548.
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This paper describes a pilot study to investigate the influence of FDPs on platelet aggregation in a small cohort of patients (N = 12) undergoing systemic thrombolytic therapy with streptokinase (600,000 I.U. or 1,500,000 I.U. delivered over 30 minutes) for acute myocardial infarction.Serial pre- and post-therapy blood samples were anticoagulated with sodium citrate, and whole blood aggregation studies carried out over 24 hours using a Crono-log 540 aggregometer and the standard adenosine diphosphate (ADP), adrenalin (A), collagen (C) and ristocetin (R) aggregating agents.Results, in the form of mean percentage voltage change from baseline voltage change, measured at 8 minutes after addition of aggregant, are presented for the cohort at times in Figure 1. Serial aggregometry tracings for one representative patient are shown in Figure 2.Clearly comparison of the 1 hour and 18 hour results for each aggregating agent shows a variable but consistent return towards baseline (at FDP < 8 μg/ml) as the FDP concentration drops. This implies that, provided the same platelet population is involved, there is no generalised permanent platelet defect consequent on systemic STK therapy. Coulter counter measurements do not indicate the increase in platelet number that would suggest a large influx of new platelets.
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Longmire, K., and M. M. Frojmovic. "PLATELET AGGREGATION DYNAMICS TO ADENOSINE DIPHOSPHATE IN NON-STIRRED SUSPENSIONS: LONG-RANGEINTERACTIONS FOR HUMAN, BUT NOT RABBIT, PLATELETS." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1644464.
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The simplest experimental approach for a theoretical description of platelet aggregation is based on kinetics of early multiplet formation (‹4 platelets per aggregate)occurring with diffusion-dependent particle collisions (no flow). The Smoluchowski theory was used to calculate collision efficiencies, αβ, from a linear plot of platelet particle count (Nt)−1 vs time (t) following addition of adenosine diphosphate (ADP) to citrated platelet-rich-plasma (PRP) for 7 human (H) and 2 rabbit (R) donors. A 0.1 ml sample of PRP was stirred with ADP for 0.5s, then immediately transferred to a 37°C bath for no-stir (diffusion) studies or further stirred with ADP for stir-induced aggregation studies. Samples were fixed with 0.5 ml 0.8% glutaraldehyde with particle count (Nt) determined with a resistive counter and % aggregation (PA) computed (reproducibility/sensitivity ‹ 5%). For stir conditions, R platelets were as sensitive and as rapidly aggregated by ADP (2-10 μM) as H platelets, with ∼ 1 s time lag for onset of PA. However, for no-stir conditions, linear regression analysis of data for ADP (5-10 μM) induced PA for H platelets for 0-30 s gave αβ = 7.5±4.6 (r = 0.9±0.05). Analysis at longer “diffusion” times showed a second phase (60-300 s) in some H donors with aB = 0.5±0.4 (4/9 donors), while R platelets showed only 1 phase with αβ = 0.65±0.15 (0-60 to 0-900 s) (r = 0.8±0.1). The ADP sensitivity ([ADP]½ corresponding to 50% of maximal changes) for the abnormally rapid PA in no stir H PRP for early times, measured over 0.4-100 μM range, was found to be ∼9 μM (5-17 μM range) and 3.5 μM (3-10 μM) for measurements respectively at 5-10 and 20-30s; these values were ∼ 3-8 × greater than lADPji measured for stirred suspensions for rate/extent of PA or rate of turbidometrically-measured macroaggregation (TA), while › [ADP] threshold for secondary aggregation in TA (10 H donors). These abnormally large aB values and their ADP sensitivity observed for human platelets are consistent with long-range interactions mediated by“chemotactic” agents released from the cells but distinct from normal dense granule release requiring macroaggregation, or by as yet uncharacterized membrane or polymetric bridges.
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Herman, A. G., and H. Bult. "RED BLOOD CELL LYSIS MAY INFLUENCE PLATELET AGGREGATION IN WHOLE BLOOD AGGREGOMETER." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1644552.
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The electronic whole blood aggregometer (WBA) has the advantage that it enables the study of platelet aggregation in whole blood shortly after blood collection. Using the WBA varying results have been obtained with respect to the anti-aggregating activity of dipyridamole. As dipyridamole is an efficient inhibitor of adenosine uptake, we tested whether the degree of red blood cell lysis (and thus availability of adenine nucleotides) affected its efficacy. Citrate (10.7 mM) blood was stored in sealed tubes and used between 20 and 100 min after venipuncture. One ml was placed in a Chronolog Model 540 WBA together with 10 μl 0.9 % NaCl, dipyridamole (final conc. 3, 10 or 30 μM) or its solvent (final conc. 0.03, 0.1 or 0.3 %). After reaching a stable baseline and WBA calibration, aggregation was induced by injection of 10 μM ADP dissolved in 10 μl 0.9 % NaCl (one channel) or 10 μl distilled water (other channel). Maximum impedance increase in 10 min was measured, red blood cells were removed by centrifugation, and from microhematocrit and absorbance at 416 nm the volume of lysed packed red blood cells was estimated. ADP caused aggregation (12.9 ± 1.9 and 11.1 ± 0.8, Ohm) and there was red blood cell lysis (2.8 ± 0.5 and 0.8 ± 0.2 μl red blood cells, ADP resp. in H20 and 0.9 % NaCF, n = 6). Dipyridamole (30 μM) suppressed aggregation when compared with solvent, but only when ADP was given in H20 (reduction resp. 4.4 ± 1.4 and 1.9 ± 1.6 ohm). Moreover, there was a negative correlation between the degree of haemolysis and the aggregation response at 10 as well as 30 μM dipyridamole. This reduced aggregation with increasing haemolysis was not observed in the presence of the corresponding solvent concentrations. The red blood cell lysis was proportional to the plasma ATP (luciferine-luciferase method) concentration as an index of adenine nucleotide leakage. In conclusion, a certain degree of haemolysis caused by stirring and injection with a microsyringe is inherent to the WBA, but use of hypotonic vehicles should be avoided. Release of red blood cell constituents may affect platelet aggregation as such, or interfere with the activity of adenosine uptake inhibitors and possibly other drugs. It may help to explain some of the variable results obtained with dipyridamole.
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Patel, R., and R. Bick. "PLATELET DYSFUNCTION INDUCED BY TETRAHYDROCANNABINOL." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1644877.
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Many drugs and other agents have been reported to induce platelet dysfunction and clinical bleedability; however, tetrahydrocannabinol (marijuana) has thus far not been reported. The patient herein described is a 28-year-old Caucasian female who wasreferred for evaluation of easy and spontaneous bruising. On history, the patient related that for a three-month period she had been developing spontaneous ecchymoses of the extremities and torso. She denied any medication other than heavy marijuana use. Hemostasis evaluation revealed her to have a normal prothrombin time, partial thromboplastin time (PTT), Factor VIII coagulant activity (Factor VIII:C), Factor VIII related antigen (Factor VIII:RAg), and ristocetincofactor activity. Platelet aggregation was performed which revealed abnormal aggregation to epinephrine, adenosine diphosphate (ADP) and abnormal release but normal aggregation toristocetin. She was asked to refrainfrom marijuana and was reaggregated revealing normal aggregation and release to epinephrine, ADP, collagen and arachidonic acid; however, ADP release induced by ristocetin remainedmoderately abnormal, even though aggregation was normal. In addition, with cessation of marijuana use, her clinical bruising abated.Following this, she again indulged in marijuana and she was reaggregated, revealing delayed aggregation and release to epinephrine with abnormal aggregation to ADP. Additionally, ristocetin release and adenosine triphosphate (ATP) release remained abnormal but aggregation remained normal and arachidonic acid aggregationremained normal.In summary, we herein describe a young female who demonstrated aggregation abnormalities and clinically significant spontaneous bruising during periods of using marijuana; the defect disappeared upon cessation of marijuana and reappeared upon resumption of marijuana use. The defect atpresent appears to be that of a membrane-type defect with no evidence that marijuana interferes with the prostaglandin pathway.
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Gentry, P. A., and G. S. Bondy. "The aggregation of bovine platelets is not dependent on thromboxane B2 production." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1644500.
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Bovine and human platelets appear to be equally sensitive to inhibition by several environmental toxins even though the bovine is not generally recognised as a species prone to thromboembolic and hemorrhagic disease. During the examination of the mechanism of action of the toxins it became necessary to establish parameters for normal bovine platelet function.Bovine platelets suspended in homologous plasma demonstrate various responses to different agonists. Bovine platelets aggregate effectively and irreversibly to fibrillar form collagen and adenosine-diphosphate (ADP), undergo reversible aggregation in response to platelet activating factor (PAF), exhibit a minimal aggregation response to serotonin (5HT) and arachidonic acid (AA) and are refractory to acid-soluble collagen (calf skin). A synergistic aggregation response is observed with the combination of ADP and 5HT, an additive response with ADP and PAF, while the addition of AA has no effect on the ADP induced aggregation response. A biphasic response has not been observed with any of the agonists or with the combinations of agonists. There is no direct correlation between the maximum aggregation response induced by ADP and PAF and the amount of thromboxane B2 (TXB2) released from the stimulated platelets. Similarly when acetylsalicylic acid (ASA) is added to the platelet suspensions, TBXg release can be completely inhibited without any observable effect on the aggregation response. Platelet aggregation was also unaffected by indomethacin and dipyridamole. Verapamil is a weak inhibitor of ADP induced aggregation but is a potent inhibitor of PAF stimulated platelets. Bovine platelets appear to have some distinct characteristics since they exhibit some responses which are not only different from human platelets but are also different from platelets obtained from other large animals such as the sheep and horse.
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Ortega, M. P., C. Sunkel, and J. G. Priego. "INHIBITION OF HUMAN PLATELET FUNCTION BY PCA-4230." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1643431.
Full textAbstract:
PCA-4230 (3-{2-(N-l,2-benzisothiazolyl-3(2H)one-1,1-dioxide) ethoxycarbonyl}-2,6-dimethyl-5-ethoxycarbonyl-4-methyl-l,4-dihy-dropyridine) is a new synthetic compound which has been selected after evaluation of .several series of molecules included in an ex tensive program of synthesis and biological screening.The purpose of this study was to investigate the In vUjiO effects of PCA-4230 on human platelet function.Platelet aggregation (PA) was measured, in platelet rich plasma (PRP) or washed platelets, according to Born’s technique. Release reaction (RR) was measured by the luminiscence method as adenosine triphosphate (ATP) release in response to stimulation. Aggregating agents were adenosine diphosphate (ADP), epinephrine (Epi), collagen (Col), thrombin (Thr), calcium ionophore (A23187) arachidonic acid (AA), thromboxane agonist (U46619) or platelet activating factor (PAF). Incubation with PCA-4230 (1 to 10 μM) we re carried out at 37°C for 15 minutes. PCA-4230 potentiation of Prostacyclin (PGI2) anti-aggregatory activity was also studied by addition to PRP of PGI2, PCA-4230 or both, and PA by ADP.PCA-4230 inhibited PA and RR in PRP in a concentration-dependent fashion when Col, Epi, U46619 or PAF were used as agonists. AA-and Thr-induced aggregation were only slightly impaired and no in hibition was shown on ADP or A23187-triggered activation. A23187-induced aggregation and RR were inhibited only in the absence of extracellular Ca++ in washed platelets. This effect was overcome by addition of Ca++ 1 mM. Additionally, the inhibitory effect of PGI2 on ADP-induced PA, was synergistically potentiated by PCA-4230, suggesting inhibitory activity of the compound on cjy clic nucleotide phosphodiesterase.Since PCA-4230 inhibited PA and RR induced by Epi, U46619 and PAF, mediated viareceptor-agonist binding, and Col-inducedactivation, it is reasonable to suspect that common process(es) may be involved. Recently, it has been suggested that intraplatelet Ca++ levels, actingas a second messenger, are directly linked to the d<2 gree of platelet activation.Therefore, the ability of PCA-4230 to modulate platelet function appears, at leastin part, to be due to regulation of cytosolic Ca++ levels. This hypothesis is confii: med by the results with A23187-induced aggregation in absence of extracellular Ca++.
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Saniabadi, A. R., G. D. O. Lowe, and C. D. Forbes. "EFFECT OF DIPYRIDAMOLE ON SPONTANEOUS PLATELET AGGREGATION IN WHOLE BLOOD DECREASES WITH THE TIME AFTER VENEPUNCTURE:EVIDENCE FOR THE ROLE OF ADP." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1644819.
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Spontaneous platelet aggregation (SPA) was studied in human whole blood at 3,5, 10, 20, 30, 40 and 60 minutes after venepuncture. Using a whole blood platelet counter (Ultra Flo 100), SPA was quantified by measuring the fall in single platelet count upon rollermixing aliquots of blood at 37°C. The extent of SPA increased with the time after venepuncture, with a correlation coefficient of 0.819. The inhibitory effect of dipyridamole (Dipy) on SPA was studied: (a) 10-5M at each time interval; (b) 0.5-100 x 10-6M at 3 and 30 minutes, and (c) 15 x 10-6M in combination with 2 x 10-4M adenosine (Ad), 8 x 10-6M 2-chloradenosine (2ClAd, a specific ADP receptor blocker) and 5 x 10-5M aspirin. There was a rapid decrease in the inhibitory effect of Dipy with the time after venepuncture; the correlation coefficient was -0.533. At all the concentrations studied, Dipy was more effective at 3 minutes than at 30 minutes after venepuncture. A combination of Dipy withAd, 2ClAd or aspirin was a more effective inhibitor of SPA than either drug alone. However, when an effective concentration of Dipy and an ineffective concentration of Ad (10-4M) were addedtogether, the inhibitory effect of Dipy was not increased, suggesting that Dipy inhibits platelet aggregation independent of Ad.The increase in SPA with the time after venepuncture was abolished when bloodwas taken directly into the anticoagulant containing 2ClAd (5 x 10-6M). We conclude that ADP released from the red blood cells is responsible for the increased platelet aggregability with the time after venepuncture, and makes a serious contribution to the artifacts ofin vitro platelet function studies. Furthermore, the decrease in the inhibitory action of Dipy with the time after venepuncture may explain why previously, it has not been possible to observe inhibition of platelet aggregation by Dipy in platelet rich plasma which requires time to prepare.
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Sakariassen, S. K., E. Fressinaud, D. Meyer, J. J. Sixma, and R. H. Baumgartner. "RHEOLOGY AND PLATELET-SURFACE ADHESION." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1643987.
Full textAbstract:
The process of platelet adhesion to sites of vascular injury is pivotal for the arrest of bleeding. The same process may, on the other hand, lead to formation of mural thrombi and may play a role in atherogenesis through the release of platelet-derived growth factor. The events of platelet-surface adhesion may be divided into initial attachment and the subsequent spreading on the surface. These interactions are mediated by a variety of factors, including glycoproteins (GP) in the platelet membrane, von Willebrand factor (vWF) in plasma, and the composition of the surface.However, in most instances their effects on adhesion are dependent on the shear rate.We have investigated the importance of some of these factors in flowing blood at shear rates ranging from those present in large arteries (≃ 200 sec-1) to those present in the microcirculation (≃2600 sec-1). We used annular- and parallel-plate-perfusion chambers with de-endothelial-ized human arteries and collagen-coated surfaces, respectively. A highly reactive surface, such as formed by collagen fibrils, triggers rapid platelet adhesion and thrombus growth on the upstream portion of the surface. This rapid consumption of platelets depletes the boundary layer of the blood flow of platelets, resulting in fewer platelets to adhere further downstream. This effect is most pronounced at shear rates below 650 sec-1, i.e., at conditions with low radial transport of platelets. This phenomenon, apparently physical in nature, we have termed "axial dependence."Deficiency of GPIb results in impaired initial attachment of platelets to subendothelium, a defect which virtually abolishes initial attachment at shear rates above 500 sec-1. However, inhibition of binding of ADP to its putative 100Kd GP receptor by the adenosine analogue 5'-p-fluoro-sulfonyl-adenosine completely prevents initial attachment of platelets. Conversely, deficiency of GPIIb/IIIa results in partially impaired platelet spreading (20-50%), but only at shear rates above 1000 sec-1; deficiency of GPIa results in no platelet spreading, independent of the shear rate. The importance of GPIb and GPIIb/IIIa in adhesion was further demonstrated by experiments using monoclonal antibodies to either GPIb or GPIIb/IIIa.Addition of these antibodies to blood from healthy subjects duplicates the effects found in the natural deficiency states. Furthermore, we used two monoclonal antibodies to vWF, which specifically inhibit either ristocetin-induced binding of vWF to GPIb or thrombin/ADP-induced binding of vWF to GPIIb/IIIa. Each of these antibodies inhibits ≃ 90% of adhesion at 2600 sec-1 shear rate, while no effect is seen at 650 sec-1. Inhibition of binding of vWF, fibronectin, and fibrinogen to GPIIb/IIIa by a dodecapeptide of the γ-carboxy terminus of fibrinogen inhibits ≃ 30% of adhesion in normal blood at 2600 sec-1 shear rate. No effect is present at 650 sec-1 shear rate.These experiments indicate that (1) ADP and/or its putative receptor and GPIb are involved in the early phase of adhesion, whereas (2) GPIa and GPIIb/IIIa are involved in the spreading reaction. It is also apparent that (3) GPIb and GPIIb/IIIa act as receptors for vWF in the process of bridging the platelet to sites of vascular injury, and that (4) vWF is required for both initial attachment and spreading. (5) The shear rate has an unambiguous role in these complex interactions and in the "axial dependence" phenomenon.
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Burroughs, A., L. Taylor, D. Sprengers, R. A. Hatton, N. McIntyre, and P. BA Kernoff. "HAEMOSTATIC CHANGES IN CIRRHOSIS AFTER REPEATED DOSES OF DESAMINO D-ARGININE VASOPRESSIN (DDAVP)." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1644128.
Full textAbstract:
Eight patients with stable cirrhosis received DDAVP (0.3ug/kg I. V. of Desmopressin acetate, Ferring Pharmaceuticals) and this dose was repeated after 4h and 24h. Blood for haemostatic studies was collected immediately before and lh after each dose. Results, shown below as medians (expressed in u/dl), with ranges in parentheses, were analysed using the Wilcoxon signed rank test for paired data. One hour after the first dose, von Willebrand factor antigen (VW:ag) and Ristocetin co-factor activity (Ricof) rose from 380 (182-1060) to 502 (230-1000), p<0.01 and from 400 (154-1200) to 494 (180-1600), p<0.01 respectively. This rise was sustained at 4h but increased further lh after the second dose: VW:ag to 540 (305-1000) and Ricof to 570 (420-1150), p<0.01. Levels were significantly above baseline (p<0.01) at 24h but rose again after the third dose: VW:ag to 540 (300-1180), p=<0.01 and Ricof to 479 (277-625). A similar but less marked response was seen in factor VIII:C from 220 (112-300) to 300 (128-360) p= 0.01 at lh, which was maintained up to 4h but not 24h. The rise after the second and third dose was not significant. Multimeric analysis of VWF showed an increase in the very high MW oligomers after DDAVP. Irrespective of the basal value, the euglobulin lysis time shortened consistently after DDAVP and platelet aggregation showed an enhancement with ristocetin, a decrease with adrenaline and no change with adenosine diphosphate and collagen. The bleeding time shortened in half the patients but did not correlate with other changes. We conclude that rises in VW:ag and Ricof are sustained with repeated doses of DDAVP despite the high initial levels in cirrhotics, whereas rises in VIII:C and fibrinolytic activity are transient.